Anti-microbial articles and methods of using same

ABSTRACT

An article having anti-microbial effect is provided. The article includes an occlusive layer; a substrate having two opposing major surfaces, wherein one opposing major surface is a nanostructured surface; a metal oxide layer, wherein the nanostructured surface is coated with the metal oxide layer and the metal oxide layer comprises a metal oxide; and a metal layer overlaying the metal oxide layer.

BACKGROUND

The risk of being infected from medical devices is particularly high inthe medical field. Anti-microbial articles or coatings are usedextensively to prevent/reduce infections in the medical community. Forexample, medical devices used by doctors, including orthopedic pins,plates and implants, wound dressings, etc., must constantly guardagainst infection. Metallic ions with anti-microbial properties, such asAg, Au, Pt, Pd, Ir, Cu, Sn, Sb, Bi and Zn, were used as anti-microbialcompounds. Of these metallic ions, silver is known due to its goodbioactivity. Various silver salts, complexes and colloids have been usedto prevent and control infection.

SUMMARY

Although soluble salts of silver have been currently used to preventmicrobial infections, they do not provide prolonged release of silverions due to loss through removal or complexation of the free silverions. They must be reapplied periodically to address this problem.Sometimes, reapplication is burdensome or sometimes even impractical,for example, when implanted medical devices are involved. Thus, it isdesirable to have an anti-microbial article to provide a more effectiverelease of anti-microbial agents.

In various exemplary embodiments described herein, the disclosedarticles may be used to prevent microbial infections. The disclosedarticles may be useful to provide an enhanced release of anti-microbialagents and thus to provide an increased anti-microbial activity.

In one aspect, the disclosure provides an article that includes anocclusive layer; a substrate having two opposing major surfaces, whereinone opposing major surface is a nanostructured surface; a metal oxidelayer, wherein the nanostructured surface is coated with the metal oxidelayer and the metal oxide layer comprises a metal oxide; and a metallayer overlaying the metal oxide layer.

In another aspect, the disclosure provides an article that includes anocclusive layer; a substrate having two opposing major surfaces, whereinone opposing major surface is a nanostructured surface; a metal layer,wherein the nanostructured surface is coated with the metal layer; and ametal oxide layer overlaying the metal layer, wherein the metal oxidelayer comprises a metal oxide.

Some other aspects of the present disclosure provide a method of usingthe article. The method can include providing the article of the presentdisclosure and applying the article to a subject; wherein the articleexhibits a more than 4 log reduction of bacterial growth within 7 days.

Other features and aspects of the present disclosure will becomeapparent by consideration of the detailed description.

Definitions

Certain terms are used throughout the description and the claims that,while for the most part are well known, may require some explanation. Itshould be understood that, as used herein:

The terms “about” or “approximately” with reference to a numerical valueor a shape means+/−five percent of the numerical value or property orcharacteristic, but also expressly includes any narrow range within the+/−five percent of the numerical value or property or characteristic aswell as the exact numerical value. For example, a temperature of “about”100° C. refers to a temperature from 95° C. to 105° C., but alsoexpressly includes any narrower range of temperature or even a singletemperature within that range, including, for example, a temperature ofexactly 100° C.

The terms “a”, “an”, and “the” include plural referents unless thecontent clearly dictates otherwise. Thus, for example, reference to amaterial containing “a compound” includes a mixture of two or morecompounds.

The term “or” is generally employed in its sense including “and/or”unless the content clearly dictates otherwise.

The term “wetting time” refers to the time period between when a drop ofcolored water is added to the surface of an article and when the waterdrop is completely absorbed into the article.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure may be more completely understood in consideration of thefollowing detailed description of various embodiments of the disclosurein connection with the accompanying drawings, in which it is to beunderstood by one of ordinary skill in the art that the drawingsillustrate certain exemplary embodiments only, and are not intended aslimiting the broader aspects of the present disclosure.

FIG. 1 is a cross-sectional view of an embodiment of an anti-microbialarticle of the present disclosure.

FIG. 2 is a cross-sectional view of an embodiment of an anti-microbialarticle of the present disclosure.

FIG. 3 is a schematic view of an exemplary substrate with ananostructured surface.

DETAILED DESCRIPTION

In the following description, reference is made to the accompanying setof drawings that form a part of the description hereof and in which areshown by way of illustration several specific embodiments. It is to beunderstood that other embodiments are contemplated and may be madewithout departing from the scope or spirit of the present invention. Thefollowing detailed description, therefore, is not to be taken in alimiting sense.

Unless otherwise indicated, all numbers expressing feature sizes,amounts, and physical properties used in the specification and claimsare to be understood as being modified in all instances by the term“about.” Accordingly, unless indicated to the contrary, the numericalparameters set forth in the foregoing specification and attached claimsare approximations that can vary depending upon the desired propertiessought to be obtained by those skilled in the art utilizing theteachings disclosed herein. At the very least, and not as an attempt tolimit the application of the doctrine of equivalents to the scope of theclaimed embodiments, each numerical parameter should at least beconstrued in light of the number of reported significant digits and byapplying ordinary rounding techniques. In addition, the use of numericalranges with endpoints includes all numbers within that range (e.g. 1 to5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5) and any narrower range orsingle value within that range.

Various exemplary embodiments of the disclosure will now be describedwith particular reference to the Drawings. Exemplary embodiments of thepresent disclosure may take on various modifications and alterationswithout departing from the spirit and scope of the disclosure.Accordingly, it is to be understood that the embodiments of the presentdisclosure are not to be limited to the following described exemplaryembodiments, but are to be controlled by the limitations set forth inthe claims and any equivalents thereof.

An article is disclosed herein. FIG. 1 is a cross-sectional view of anembodiment of article 1. Overall, article 1 includes an occlusive layer10, a substrate 20 overlaying the occlusive layer, a metal oxide layer30 overlaying the substrate and a metal layer 40 overlaying the metaloxide layer. The substrate 20 has two opposing major surfaces. Oneopposing major surface of substrate 20 often is a nanostructuredsurface, which is provided with a nanostructure 25. In the embodimentshown in FIG. 1, metal oxide layer 30 adjoins the nanostructured surfacewith the nanostructure 25 and metal layer 40 is next to metal oxidelayer 30. Alternatively, metal layer can adjoin the nanostructuredsurface with the nanostructure and metal oxide layer is next to metallayer. The article may include an optional insulation coating layer 45between metal oxide layer 30 and metal layer 40. Insulation coatinglayer can cover entire or part of metal layer. In some embodiments, themetal layer can be discontinuous or patterned, for examples as shown inFIG. 1.

Alternatively, as shown in FIG. 2, the metal oxide layer 30 can be indirect contact nanostructured surface 25 of the substrate 20 and themetal layer 40 can be in direct contact with the other opposing majorsurface of the substrate 20. In this embodiment, the metal layer can bediscontinuous or continuous.

An additional adhesive layer 50 can be supplied to article 1 as shown inFIG. 1. In this embodiment, adhesive layer 50 covers the entire surfaceof metal layer 40. However, it is understood that the adhesive layer 50may cover only a portion of the metal layer 40. The article may includean optional release liners (not shown) that covers all or a portion ofthe adhesives to prevent contamination of the adhesives. An optionalcarrier (not shown) may be included to cover all or a portion ofocclusive layer 10, providing structural support if the article is thinand highly flexible. The carrier may be removable from occlusive layer10 once the article is placed on a subject.

The article of the present disclosure can be used to provide ananti-microbial effect. The article can be provided to a health careprovider and can be applied to a subject to release anti-microbialagents.

Occlusive Layer

The occlusive layers are useful to provide an impermeable barrier to thepassage of liquids and at least some gases. Representative barriers mayinclude non-woven and woven fibrous webs, knits, films, foams polymericfilms and other familiar backing materials. In some embodiments, atransparent occlusive layer is desirable to allow for viewing of theunderlying subjects. Suitable occlusive layers may include thosedescribed in International Publication No. WO 2014/149718, thedisclosures of which are hereby incorporated by reference.

In one embodiment, the occlusive layer has high moisture vaporpermeability, but generally impermeable to liquid water so that microbesand other contaminants are sealed out from the area under the article.One example of a suitable material is a high moisture vapor permeablefilm such as described in U.S. Pat. Nos. 3,645,835 and 4,595,001, thedisclosures of which are herein incorporated by reference. In oneembodiment, the occlusive layer can be an elastomeric polyurethane,polyester, or polyether block amide films. These films combine thedesirable properties of resiliency, elasticity, high moisture vaporpermeability, and transparency. A description of this characteristic ofocclusive layers can be found in issued U.S. Pat. Nos. 5,088,483 and5,160,315, the disclosures of which are hereby incorporated by reference

Commercially available examples of potentially suitable materials forthe occlusive layer may include the thin polymeric film sold under thetrade names TEGADERM (3M Company), OPSITE (Smith & Nephew), etc. Becausefluids may be actively removed from the sealed environments defined bythe article, a relatively high moisture vapor permeable occlusive layermay not be required. As a result, some other potentially usefulmaterials for the occlusive layer may include, e.g., metallocenepolyolefins and SBS and SIS block copolymer materials could be used.

Regardless, however, it may be desirable that the occlusive layer bekept relatively thin to, e.g., improve conformability. For example, theocclusive layer may be formed of polymeric films with a thickness of 200micrometers or less, or 100 micrometers or less, 50 micrometers or less,or 25 micrometers or less.

Substrate with a Nanostructured Surface

FIG. 3 is a schematic view of an exemplary substrate with ananostructured surface. The nanostructured surface 602 of substrate 600typically can comprise nanostructures (nanoscale features) 605 ofdiverse height and aspect ratio. Generally, the nanostructured surfacecan have a nanostructured anisotropic surface. The nanostructuredanisotropic surface typically can comprise nanoscale features. In someembodiments, the nanostructured anisotropic surface can compriseanisotropic nanoscale features. In some embodiments, the nanostructuredanisotropic surface can comprise random anisotropic nanoscale features.The nanostructured anisotropic surface typically can comprise nanoscalefeatures having a height to width ratio (aspect ratio) about 2:1 orgreater; preferably about 5:1 or greater. In some embodiments, theheight to width ratio can even be 50:1 or greater, 100:1 or greater, or200:1 or greater. The nanostructured anisotropic surface can comprisenanoscale features such as, for example, nano-pillars or nano-columns,or continuous nano-walls comprising nano-pillars or nano-columns.Typically, the nanoscale features have steep side walls that aresubstantially perpendicular to the substrate.

The substrate with the nanostructured surface can be formed by anysuitable means, including plasma treatment process. Suitable process caninclude those described in U.S. Pat. Nos. 5,888,594, 8,460,568,8,634,146 and International Publication No. WO 2015/013387, thedisclosures of which are hereby incorporated by reference.

The substrate can be made of any material that can be etched by themethods disclosed in U.S. Pat. Nos. 5,888,594, 8,460,568, 8,634,146 andInternational Publication No. WO 2015/013387. The substrate can be anabsorbent substrate selected from foam, fabric, nonwoven, hydrocolloid,hydrogel, and combination of thereof. Exemplary absorbent substrate caninclude film, fabrics or porous article made from viscose, rayon,alginate, gauze, biopolymers, polyurethane, biodegradable polymers orthe polymers described in U.S. Pat. No. 7,745,509, the disclosures ofwhich is hereby incorporated by reference. The absorbent materials usedin the absorbent substrate can be manufactured of any suitable materialsincluding, but not limited to, woven or nonwoven cotton or rayon.Absorbent pad can be used as the absorbent layer and can be useful forcontaining a number of substances, optionally including drugs fortransdermal drug delivery, chemical indicators to monitor hormones orother substances in a patient, etc.

The absorbent layer may include a hydrocolloid composition, includingthe hydrocolloid compositions described in U.S. Pat. Nos. 5,622,711 and5,633,010, the disclosures of which are hereby incorporated byreference. The hydrocolloid absorbent may comprise, for example, anatural hydrocolloid, such as pectin, gelatin, or carboxymethylcellulose(CMC) (Aqualon Corp., Wilmington, Del.), a semi-synthetic hydrocolloid,such as cross-linked carboxymethylcellulose (X4ink CMC) (e.g. Ac-Di-Sol;FMC Corp., Philadelphia, Pa.), a synthetic hydrocolloid, such ascross-linked polyacrylic acid (PAA) (e.g., CARBOPOL™ No. 974P; B.F.Goodrich, Brecksville, Ohio), or a combination thereof. Absorbent layercan be manufactured of other synthetic and natural hydrophilic materialsincluding polymer gels and foams.

Metal Oxide Layer

The metal oxide layer of the present disclosure includes a metal oxide.The metal oxide can be those known to have an anti-microbial effect. Formost medical use, the metal oxide can also be biocompatible. In someembodiments, the metal oxide used in the metal oxide layer can include,but is not limited to, silver oxide, copper oxide, gold oxide, zincoxide, magnesium oxide, titanium oxide, chromium oxide and combinationsthereof. In some of these embodiments, the metal oxide can be silveroxide, including but not limited to, Ag₂O. In some embodiments, themetal oxide layer can include less than 40 wt. %, less than 20 wt. %,less than 10 wt. %, less than 5 wt. %, less than 1 wt. % non-oxidizedmetal. When the metal oxide layer includes more than 40 wt. %non-oxidized metal, the article will become more conductive, i.e., theresistivity of the article decreases, and the release of anti-microbialagents also decreases.

The metal oxide layer can be formed by any suitable means, for example,by physical vapor deposition techniques. The physical vapor depositiontechniques can include, but is not limited to, vacuum or arcevaporation, sputtering, magnetron sputtering and ion plating. Suitablephysical vapor deposition techniques can include those described in U.S.Pat. Nos. 4,364,995; 5,681,575 and 5,753,251, the disclosures of whichare hereby incorporated by reference.

By the controlled introduction of reactive material, for example, oxygeninto the metal vapor stream of vapor deposition apparatus during thevapor deposition of metals onto substrates, controlled conversion of themetal to metal oxides can be achieved. Therefore, by controlling theamount of the reactive vapor or gas introduced, the proportion of metalto metal oxide in the metal oxide layer can be controlled. For 100%conversion of the metal to metal oxides at a given level of the layer,at least a stoichiometric amount of the oxygen containing gas or vaporis introduced to a portion of the metal vapor stream. When the amount ofthe oxygen containing gas increases, the metal oxide layer will containa higher weight percent of metal oxide. The ability to achieve releaseof metal atoms, ions, molecules or clusters on a sustainable basis canbe effected by varying the amount of the oxygen containing gas. As theamount of metal oxide increases when the level of oxygen containing gasintroduced increases, metal ions released from the article in turnincreases. Thus, a higher weight percent of metal oxide can, forexample, provide an enhanced release of anti-microbial agents, such asmetal ions and provide an increased anti-microbial activity.

The metal oxide layer can be formed as a thin film. The film can have athickness no greater than that needed to provide release of metal ionson a sustainable basis over a suitable period of time. In that respect,the thickness will vary with the particular metal in the coating (whichvaries the solubility and abrasion resistance), and with the amount ofthe oxygen containing gas or vapor introduced to the metal vapor stream.The thickness will be thin enough that the metal oxide layer does notinterfere with the dimensional tolerances or flexibility of the articlefor its intended utility. Typically, the metal oxide layer has athicknesses of less than 1 micron. However, it is understood thatincreased thicknesses may be used depending on the degree of metal ionrelease needed over a period of time.

Metal Layer

The metal layer of the present disclosure includes a metal. The metalcan be those known to have a positive electric potential. In someembodiments, the metal oxide used in the metal oxide layer can include,but is not limited to, zinc, magnesium, aluminum, iron, calcium, tin,copper, titanium, chromium, nickel and alloys thereof. The metal oxidelayer can be formed by any suitable means, for example, by vapordeposition techniques. The vapor deposition techniques can include, butis not limited to, vacuum or arc evaporation, sputtering, magnetronsputtering and ion plating. Suitable physical vapor depositiontechniques can include those described in U.S. Pat. Nos. 4,364,995;5,681,575 and 5,753,251, the disclosures of which are herebyincorporated by reference.

Optional Components

Suitable polymer for use in the insulation coating layer can includepolyethylene terephthlate, polystyrene, acrlonitrile butabiene styrene,polyvinyl chloride, polyvinylidene chloride, polycarbonate,polyacrylates, polyurethanes, polyvinyl acetate, polyvinyl alcohol,polyamide, polyimide, polypropylene, polyester, polyethylene,poly(methyl methacrylate), polyethylene naphthalate, styreneacrylonitrile copolymer, silicone-polyoxiamide polymers, fluoropolymers,cellulose triacetate polymer, cyclic olefin copolymers and thermoplasticelastomers. The insulation coating layer can be formed by any suitablemeans, including extrusion, solvent casting, or lamination processdescribed in U.S. Pat. No. 3,415,920, U.S. Pat. No. 4,664,859 and U.S.Pat. No. 3,416,525.

Suitable adhesive for use in the article includes any adhesive thatprovides acceptable adhesion to skin and is acceptable for use on skin(e.g., the adhesive should preferably be non-irritating andnon-sensitizing). Suitable adhesives are pressure sensitive and incertain embodiments have a relatively high moisture vapor transmissionrate to allow for moisture evaporation. Suitable pressure sensitiveadhesives include those based on acrylates, urethane, hyrdogels,hydrocolloids, block copolymers, silicones, rubber based adhesives(including natural rubber, polyisoprene, polyisobutylene, butyl rubberetc.) as well as combinations of these adhesives. The adhesive componentmay contain tackifiers, plasticizers, rheology modifiers as well asactive components including for example an antimicrobial agent. Suitableadhesive can include those described in U.S. Pat. Nos. 3,389,827;4,112,213; 4,310,509; 4,323,557; 4,595,001; 4,737,410; 6,994,904 andInternational Publication Nos. WO 2010/056541; WO 2010/056543 and WO2014/149718, the disclosures of which are hereby incorporated byreference.

Suitable release liners can be made of kraft papers, polyethylene,polypropylene, polyester or composites of any of these materials. In oneembodiment, the package that contains the adhesive dressing may serve asa release liner. In one embodiment, the liners are coated with releaseagents such as fluorochemicals or silicones. For example, U.S. Pat. No.4,472,480, the disclosure of which is hereby incorporated by reference,describes low surface energy perfluorochemical liners. In oneembodiment, the liners are papers, polyolefin films, or polyester filmscoated with silicone release materials.

The carrier used in the article can be constructed of any suitablematerials such as fabric that are woven or kitted, nonwoven material,papers, or film. In one embodiment, the carrier is along the perimeterof the occlusive layer and is removable from the occlusive layer,similar to the carrier used the 3M Tegaderm™ Transparent Film Dressing,available from 3M Company, St. Paul, Minn.

Properties

The anti-microbial effect of the article can be achieved, for example,when the article is brought into contact with an alcohol or a waterbased electrolyte such as, a body fluid or body tissue, thus releasingmetal ions such as Ag⁺, atoms, molecules or clusters. The concentrationof the metal which is needed to produce an anti-microbial effect willvary from metal to metal. Generally, anti-microbial effect is achievedin body fluids such as plasma, serum or urine at concentrations lessthan 10 ppm. In some embodiments, Ag⁺ release concentration from thearticle can be 0.1 ppm, 0.5 ppm, 1 ppm, 2 ppm, 2.5 ppm, 3 ppm, 4 ppm, 5ppm, 6 ppm, 7 ppm, 8 ppm, 9 ppm, 10 ppm, 20 ppm, 40 ppm or a rangebetween and including any two of these values. As discussed above, whenthe amount of metal oxide in the metal oxide layer increases, the metalions released from the article in turn increases. For example, a morethan 60 wt. % metal oxide provides an enhanced release of metal ionsfrom the article. Therefore, the article of the present disclosure canprovide a very effective anti-microbial effect. In some embodiments, thearticle can exhibit a more than 4 log reduction of bacterial growthwithin 7 days.

The can generate at least one electrical current when introduced to anelectrolytic solution. In the presence of an electrically conductingsolution, redox reactions may take place, and thus currents may beproduced between the metal oxide layer and the metal layer. For example,when the metal oxide layer includes silver oxide and the metal layerincludes zinc, silver oxide is the cathode (positive electrode) and zincis the anode (negative electrode), because the electrons follow fromzinc to silver oxide. The flow of ions generates the electrical current.Thus, when the article of the present application is used as a wounddressing, it can recreate a physiologic current, which is important tothe induction of neutrophil, macrophage and fibroblast cells essentialto the healing process. In addition, the current can stimulates regionalnerve endings to promote their involvement in wound resolution.

In some embodiments, the article of the present disclosure can have amore than 50%, more than 100%, more than 150%, more than 200%, more than300%, more than 400%, more than 500%, or more than 600% absorbency.Absorbency of the article generally relates to the capacity of absorbingwound fluid (exudate), when the article is used as a medical dressing.Articles with a high absorbency can absorb more exudate. This can, forexample, help decrease the risk of maceration and irritation to thewound and surrounding tissues and the frequency of replacing thearticles. In some embodiments, the article of the present disclosure canhave a less than 3 minutes, less than 2 minutes, or less than 1 minutewetting time. Wetting time of the article generally relates to theabsorption rate of fluid into the article. Shorter wetting time canenhance the overall fluid management profile, for example, increasingthe timer interval between replacing the articles. At the early stage ofhealing a wound, the article with a shorter wetting time can quicklyremove fluid, which in turns minimizes the potential risk of infection.

Various exemplary embodiments of the present disclosure are furtherillustrated by the following listing of embodiments, which should not beconstrued to unduly limit the present disclosure:

EMBODIMENTS

1. An article comprising:

-   -   an occlusive layer;    -   a substrate having two opposing major surfaces, wherein one        opposing major surface is a nanostructured surface;    -   a metal oxide layer, wherein the nanostructured surface is        coated with the metal oxide layer and the metal oxide layer        comprises a metal oxide; and    -   a metal layer overlaying the metal oxide layer.        2. An article comprising:    -   an occlusive layer;    -   a substrate having two opposing major surfaces, wherein one        opposing major surface is a nanostructured surface;    -   a metal layer, wherein the nanostructured surface is coated with        the metal layer; and    -   a metal oxide layer overlaying the metal layer, wherein the        metal oxide layer comprises a metal oxide.        3. The article of any of embodiments 1 to 2, wherein the metal        layer adjourns the metal oxide layer.        4. The article of any of embodiments 1 to 3, wherein the metal        layer is discontinuous or patterned.        5. The article of any of embodiments 1 to 2, wherein the metal        oxide layer is in direct contact with one opposing major surface        of the substrate and the metal layer is in direct contact with        the other opposing major surface of the substrate.        6. The article of any embodiments 1 to 5, wherein the        nanostructured surface comprises an anisotropic nanostructure.        7. The article of any of embodiments 1 to 6, wherein the metal        oxide is selected from silver oxide, copper oxide, gold oxide,        platinum oxide, zinc oxide, magnesium oxide, titanium oxide,        chromium oxide and combinations thereof.        8. The article of embodiment 7, wherein the metal oxide is        silver oxide.        9. The article of embodiment 8, wherein the silver oxide is        Ag₂O.        10. The article of any of embodiments 1 to 9, wherein the metal        layer comprises a metal and the metal is selected from zinc,        magnesium, aluminum, iron, calcium, tin, copper, titanium,        chromium, nickel and alloys thereof.        11. The article of any of embodiments 1 to 10, wherein the metal        oxide layer is formed by vapor deposition.        12. The article of any of embodiments 1 to 11, wherein the        article exhibits a more than 4 log reduction of bacterial growth        within 7 days.        13. The article of any of embodiments 1 to 12, wherein Ag⁺        release concentration of the article is more than 0.1 ppm.        14. The article of embodiment 13, wherein Ag⁺ release        concentration of the article is more than 2.5 ppm.        15. The article of embodiment 14, wherein Ag⁺ release        concentration of the article is more than 3 ppm.        16. The article of any of embodiments 1 to 15, wherein wetting        time of the article is less than 3 minutes.        17. The article of any of embodiments 1 to 16, wherein wetting        time of the article is less than 2 minutes.        18. The article of any of embodiments 1 to 17, wherein the        article is capable of generating at least one electrical current        when introduced to an electrolytic solution.        19. A method of use the article of any of embodiments 1 to 2,        comprising of    -   providing the article of any of embodiments 1 to 2; and    -   applying the article to a subject;    -   wherein the article exhibits a more than 4 log reduction of        bacterial growth within 7 days.

EXAMPLES

These Examples are merely for illustrative purposes and are not meant tobe overly limiting on the scope of the appended claims. Notwithstandingthat the numerical ranges and parameters setting forth the broad scopeof the present disclosure are approximations, the numerical values setforth in the specific examples are reported as precisely as possible.Any numerical value, however, inherently contains certain errorsnecessarily resulting from the standard deviation found in theirrespective testing measurements. At the very least, and not as anattempt to limit the application of the doctrine of equivalents to thescope of the claims, each numerical parameter should at least beconstrued in light of the number of reported significant digits and byapplying ordinary rounding techniques.

Unless otherwise noted, all parts, percentages, ratios, etc. in theExamples and the rest of the specification are provided on the basis ofweight. Solvents and other reagents used may be obtained fromSigma-Aldrich Chemical Company (Milwaukee, Wis.) unless otherwise noted.

Sputtering Deposition Process

Silver films were coated onto 152 mm by 152 mm substrates by magnetronphysical vapor deposition. The films were sputtered from a 76.2 mm roundsilver target in a batch coater. The substrate was placed on a substrateholder set up inside a vacuum chamber with a sputtering metal targetlocated at a height of 228.6 mm above the substrate holder. After thechamber was evacuated to 2×10-5 torr base pressure, sputter gases ofargon (71% by flow rate) and reactive oxygen (29% by flow rate) wereadmitted inside the chamber and total pressure of the chamber wasadjusted to 5 millitorr. Sputtering was initiated using a DC powersupply at a constant power level of 0.25 kilowatts. The sputteringduration was varied to produce a same coating weight per unit area of0.05 mg/cm².

Copper films were sputtered from a 76.2 mm round copper target in abatch coater. The substrate was placed on a substrate holder set upinside a vacuum chamber with a sputtering metal target located at aheight of 228.6 mm above the substrate holder. After the chamber wasevacuated to 2×10-5 torr base pressure, argon was admitted inside thechamber and total pressure of the chamber was adjusted to 1.6 millitorr.Sputtering was initiated using a DC power supply at a constant powerlevel of 0.50 kilowatts for 5 minutes and 30 seconds.

Magnesium films were sputtered from a 76.2 mm round magnesium target ina batch coater. The substrate was placed on a substrate holder set upinside a vacuum chamber with a sputtering metal target located at aheight of 228.6 mm above the substrate holder. After the chamber wasevacuated to 2×10-5 torr base pressure, argon was admitted inside thechamber and total pressure of the chamber was adjusted to 1.6 millitorr.Sputtering was initiated using a DC power supply at a constant powerlevel of 0.50 kilowatts for 15 minutes.

Nanostructure Pretreatment Process

The provided nanostructures and methods described herein were obtainedby using a homebuilt plasma treatment system described in detail in U.S.Pat. No. 5,888,594 (David et al.) with some modifications and isillustrated in FIGS. 2, 3, and 4 a and 4 b. The width of the drumelectrode was increased to 42.5 inches (108 cm) and the separationbetween the two compartments within the plasma system was removed sothat all the pumping was carried out by means of the turbo-molecularpump and thus operating at a much lower operating pressure than isconventionally done with plasma processing. Rolls of polymeric substratewere mounted within the chamber, the substrate wrapped around the drumelectrode and secured to the take up roll on the opposite side of thedrum. The unwind and take-up tensions were maintained at 3 pounds(13.3N). The chamber door was closed and the chamber pumped down to abase pressure of 0.5 millitorr. Gases such as oxygen andhexamethyldisiloxane (HMDSO) were then introduced into the chamber. Theoperating pressure was nominally 5 millitorr or 10 millitorr. Plasma wasgenerated by applying a power of 6000 watts of radio frequency energy tothe drum. The drum was rotated so that the film was transported at adesired speed for the specific treatment time as stated in the specificexample. For a piece-part substrate, the sample was either attached to aweb carrier or to the surface of drum electrode to be treated at adesired speed for the specific etching time as stated in the specificexample.

Measurement of Micro-Current

Samples were pre-wetted with Eyesaline® (Honeywell, Platteville, Wis.).Micro-current was then measured using WAVETEK DM25XT multi-meter withtwo-point probes (Wavetek, San Diego, Calif.).

Log Reduction Testing Method

The JIS Z 2801 test method (modified) (Japan Industrial Standards;Japanese Standards Association; Tokyo, JP) was used to evaluate theantibacterial activity of antibacterial of coatings. The bacterialinoculum was prepared in a solution of 1 part Nutrient Broth (NB) and499 parts phosphate buffer. A portion of the bacterial suspension (150ul) was placed onto the surface of the article and the inoculatedarticle was incubated for the specified contact time at 27+/−1° C. Afterincubation, the article was placed into 20 ml of D/E Neutralizing Broth.The number of surviving bacteria in the Neutralizing broth wasdetermined by using 3M Petrifilm.

Substrate Wetting Time (Time to Complete Immersion) Test

Wetting time was measured by adding a drop of colored water to silvercoated absorbent article and recording the time when the water drop wascompletely absorbed into the article.

Materials

Material Supplier Eyesaline ® Honeywell, Platteville, WI Viscose Fabrics(125 gsm) Fibertex, Ingleside, IL

Example 1

The viscose fabrics was one side treated with nanostructure using themethod described above for 120 seconds. Ag was deposited on thenanostructure side of the viscose fabrics using the sputtering processdescribed above at the pressure of 5 millitorr and magnesium coating wasapplied on the second side of the viscose fabrics according to themethod above. Log reduction was tested against the Ag coating side.Microcurrent, wetting time and log reduction properties are measured andreported in Table 1.

TABLE 1 Microcurrent, wetting time and log reduction results for Sample1 S. aureus Wetting Micro- ATCC6538 Log Time current Reduction (sec-(micro- CFU/cm2 Construction onds) Amp) (24 hours) Example Ag coating -3 925 5.35 1 nanostructure viscose fabrics - Mg coating

Example 2

The viscose fabrics was two side treated with nanostructure using themethod described above for 120 seconds. Ag was deposited on the firstside of the viscose fabrics using the sputtering process described aboveat the pressure of 5 millitorr and magnesium coating was applied on thesecond side of the viscose fabrics according to the method above. Logreduction was tested against the Ag coating side. Microcurrent, wettingtime and log reduction properties are measured and reported in Table 2.

TABLE 2 Microcurrent, wetting time and log reduction results for Sample2 S. aureus Wetting Micro- ATCC6538 Log Time current Reduction (sec-(micro- CFU/cm2 Construction onds) Amp) (24 hours) Example Ag coating -4 953 5.35 2 nanostructure viscose fabrics nanostructure - Mg coating

All references and publications cited herein are expressly incorporatedherein by reference in their entirety into this disclosure. Illustrativeembodiments of this invention are discussed and reference has been madeto possible variations within the scope of this invention. For example,features depicted in connection with one illustrative embodiment may beused in connection with other embodiments of the invention. These andother variations and modifications in the invention will be apparent tothose skilled in the art without departing from the scope of theinvention, and it should be understood that this invention is notlimited to the illustrative embodiments set forth herein. Accordingly,the invention is to be limited only by the claims provided below andequivalents thereof.

1. An article comprising: an occlusive layer; a substrate having twoopposing major surfaces, wherein one opposing major surface is ananostructured surface; a metal oxide layer, wherein the nanostructuredsurface is coated with the metal oxide layer and the metal oxide layercomprises a metal oxide; and a metal layer overlaying the metal oxidelayer.
 2. An article comprising: an occlusive layer; a substrate havingtwo opposing major surfaces, wherein one opposing major surface is ananostructured surface; a metal layer, wherein the nanostructuredsurface is coated with the metal layer; and a metal oxide layeroverlaying the metal layer, wherein the metal oxide layer comprises ametal oxide.
 3. The article of claim 1, wherein the metal layer adjournsthe metal oxide layer.
 4. The article of claim 1, wherein the metallayer is discontinuous or patterned.
 5. The article of claim 1, whereinthe metal oxide layer is in direct contact with one opposing majorsurface of the substrate and the metal layer is in direct contact withthe other opposing major surface of the substrate.
 6. The article ofclaim 1, wherein the nanostructured surface comprises an anisotropicnanostructure.
 7. The article of claim 1, wherein the metal oxide isselected from silver oxide, copper oxide, gold oxide, platinum oxide,zinc oxide, magnesium oxide, titanium oxide, chromium oxide andcombinations thereof.
 8. The article of claim 7, wherein the metal oxideis silver oxide.
 9. The article of claim 8, wherein the silver oxide isAg₂O.
 10. The article of claim 1, wherein the metal layer comprises ametal and the metal is selected from zinc, magnesium, aluminum, iron,calcium, tin, copper, titanium, chromium, nickel and alloys thereof. 11.The article of claim 1, wherein the metal oxide layer is formed by vapordeposition.
 12. The article claim 1, wherein the article exhibits a morethan 4 log reduction of bacterial growth within 7 days.
 13. The articleof claim 1, wherein Ag⁺ release concentration of the article is morethan 3.5 ppm.
 14. The article of claim 1, wherein the article is capableof generating at least one electrical current when introduced to anelectrolytic solution.
 15. A method of use the article of claim 1,comprising of providing the article of claim 1; and applying the articleto a subject; wherein the article exhibits a more than 4 log reductionof bacterial growth within 7 days.